Sialo-and asialoglycoconjugates on mammalian cells were found to serve as receptors for sialic acid and Gal/GalNAc reactive lectins on certain strains of oral viridans streptococci and actinomyces, respectively. Investigations initiated to examine the regulation of the expression of these receptors employed cytofluorometry to assess the binding of directly fluoresceinated Streptococcus gordonii DL1 and Actinomyces naeslundii WVU45 or plant lectins with specificities similar to that of the actinomyces lectin to HL60 cells. Incubation of HL60 cells with DMS0, an agent known to induce differentiation towards polymorphonuclear leukocytes (PMNs), resulted in a significant enhancement of bacterial binding. Similar but less dramatic results were obtained with fluoresceinated plant lectins. The specificities of the interactions were demonstrated by saccharide inhibition as well as the finding of markedly decreased or enhanced binding of the streptococci and actinomyces, respectively, to neuraminidase treated cells. In addition, a streptococcal strain and an actinomyces mutant strain lacking lectin activity failed to bind to the HL60 cells. The interactions between these bacterial adhesins and their complimentary receptors on mature PMNs stimulated the production of superoxide anions and the release of secondary granule contents. Both species of bacteria were ingested and the actinomyces were subsequently destroyed. However, five of seven strains of S. gordonii remained viable. These five strains induced endocarditis in a rat model system in which the aortic valve was damaged by catheterization. In contrast, the two S. gordonii strains that were susceptible to lectin-mediated killing produced minimal aortic valve colonization. Although other investigators have implicated binding of bacteria to fibronectin, laminin or fibrinogen and aggregation of platelets in the etiology of endocarditis, these parameters failed to correlate with the induction of the disease process. Thus, for S. gordonii, the resistance to lectin-mediated killing by PMNs appears to be a major determinant of virulence for the initiation of endocarditis.